Epigenetic silencing of Th1 chemokines shapes tumor immunity, immunotherapy and patient outcome [shEZH2]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Ilona Kryczek
PROVIDER: E-GEOD-71870 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:To define the gene profile altered by EZH2 and H3K27me3 in response to IFNg, we performed several microarrays in primary ovarian cancer cells transfected with shEZH2 or treated with GSK126. We found that 155 and 124 genes were altered by shEZH2 and GSK126 treatment, respectively, and 20 genes were increased or decreased by both shEZH2 and GSK126 treatment. Primary ovarian cancer cells were pretreated with GSK126, or transduced with a shEZH2 lentivirus, and stimulated with IFNg for 24 hours. RNA were isolated by Rneasy kit according to the manufacturer's protocol, and applied for affymetrix microarray at University of Michigan DNA Sequencing Core
2015-08-11 | E-GEOD-71869 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-08-11 | E-GEOD-71871 | biostudies-arrayexpress
Project description:To define the gene profile altered by EZH2 and H3K27me3 in response to IFNg, we performed several microarrays in primary ovarian cancer cells transfected with shEZH2 or treated with GSK126. We found that 155 and 124 genes were altered by shEZH2 and GSK126 treatment, respectively, and 20 genes were increased or decreased by both shEZH2 and GSK126 treatment.
2015-08-11 | GSE71869 | GEO
Project description:To define the gene profile altered by EZH2 and H3K27me3 in response to IFNg, we performed several microarrays in primary ovarian cancer cells transfected with shEZH2 or treated with GSK126. We found that 155 and 124 genes were altered by shEZH2 and GSK126 treatment, respectively, and 20 genes were increased or decreased by both shEZH2 and GSK126 treatment.
2015-08-11 | GSE71870 | GEO
Project description:We studied transcriptional changes by Affymetrix human microarrays in 2 DLBCL cell lines as a result of shRNA mediated knockdown of EZH2. In eukaryotes, epigenetic post-translational modification of histones is critical for regulation of chromatin structure and gene expression. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) and is responsible for repressing target gene expression through methylation of histone H3 on lysine 27 (H3K27). Over-expression of EZH2 is implicated in tumorigenesis and correlates with poor prognosis in multiple tumor types. Recent reports have identified somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The Y641 residue is the most frequently mutated residue, with 22% of GCB (Germinal Cell B-cell) DLBCL and FL harboring mutations at this site. These lymphomas exhibit increased H3K27 tri-methylation (H3K27me3) due to altered substrate preferences of the mutant enzymes. However, it is unknown whether direct inhibition of EZH2 methyltransferase activity alone will be effective in treating lymphomas carrying activating EZH2 mutations. Herein, we demonstrate that GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and dramatically inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma. Pfeiffer and KARPAS-422 cells were treated with either shRNA targeting EZH2 (shEZH2) or a non targeting control (shNTC) for 10 days.
2012-10-12 | E-GEOD-41239 | biostudies-arrayexpress
Project description:Nlrp6-/- lamina propria Ly6C-hi monocytes in response to AOM/DSS have deficient TNFα production, but increased production of other pro-inflammatory cytokines as compared to WT NLRP6 is a member of the Nod-like receptor family, whose members are involved in the recognition of microbes and/or tissue injury. NLRP6 was previously demonstrated to regulate the production of IL-18 and is important for protecting mice against chemically-induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms by which NLRP6 reduces susceptibility to colonic inflammation remain unclear. Here, we determined that NLRP6 expression is specifically upregulated in Ly6Chi inflammatory monocytes that infiltrate into the colon during dextran sulfate sodium (DSS)-induced inflammation. Adoptive transfer of WT Ly6Chi inflammatory monocytes into Nlrp6-/- mice was sufficient to protect them from mortality, significantly reducing intestinal permeability and damage. NLRP6-deficient inflammatory monocytes were specifically defective in TNFα production, which was important for reducing DSS-induced mortality and dependent on autocrine IL-18 signaling by inflammatory monocytes. Our data reveal a previously unappreciated role for NLRP6 in inflammatory monocytes, which are recruited during intestinal injury to promote barrier function and limit bacteria-driven inflammation. This study also highlights the importance of early cytokine responses, particularly NLRP6-dependent and IL-18-dependent TNFα production in preventing chronic dysregulated inflammation. Ly6Chi monocytes were sorted from lamina propria of WT or Nlrp6-/- mice at day 10 of AOM/2%DSS. RNA was extracted and hybridized to the mouse 2.1 ST array.
2016-03-27 | E-GEOD-79631 | biostudies-arrayexpress
Project description:Nrg4 is a brown fat-enriched adipokine that binds to the liver and preserves metabolic homeostasis during chronic energy excess. Adipose tissue Nrg4 expression is reduced in mouse and human obesity. Nrg4 deficient mice develp more severe insulin resistance and hepatic fat accumulation upon high-fat diet feeding. We used microarrays to elucidate the metabolic pathways that are regulated by Nrg4 in the liver. Wild type and Neuregulin 4 (Nrg4) knockout mice were fed high-fat diet (Research Diets D12492) for eight weeks. Tissues were harvested under ad lib condition for RNA isolation and microarray hybridization using Affymetrix Mouse MG-430 PM Strip arrays. Three independent pools of WT and KO mouse liver RNA were included in the study. Manuscript title: A brown fat-enriched secreted factor preserves metabolic homeostasis through attenuating hepatic lipogenesis, (journal information TBD)
2014-11-17 | E-GEOD-53877 | biostudies-arrayexpress
Project description:Blnc1 is a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function. Blnc1 forms a ribonucleoprotein complex with transcription factor EBF2 to stimulate the thermogenic gene program. Further, Blnc1 itself is a target of EBF2, thereby forming a feedforward regulatory loop to drive adipogenesis toward thermogenic phenotype. We used microarrays to elucidate the role of Blnc1 on brown adipocyte differentiation and the induction of the thermogenic gene program. Brown adipocytes expressing vector or brown fat lncRNA 1 (blnc1) were differentiated for 6 days and harvested for RNA isolation and microarray using Affymetrix Mouse MG-430 PM Strip arrays. Two replicated samples were included in this study.
2015-02-28 | E-GEOD-55551 | biostudies-arrayexpress
Project description:Blnc1 is a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function. Blnc1 forms a ribonucleoprotein complex with transcription factor EBF2 to stimulate the thermogenic gene program. Further, Blnc1 itself is a target of EBF2, thereby forming a feedforward regulatory loop to drive adipogenesis toward thermogenic phenotype. We used microarrays to elucidate the role of Blnc1 on brown adipocyte differentiation and mitochondrial function. Brown adipocytes expressing Scramble or brown fat lncRNA 1 knockdown (shBlnc1) were differentiated for 6 days and harvested for RNA isolation and microarray using Affymetrix Mouse MG-430 PM Strip arrays. Two replicated samples were included in this study.
2015-02-28 | E-GEOD-57540 | biostudies-arrayexpress
Project description:Tendons play a critical role in the transmission of forces between muscles and bones, and chronic tendon injuries and diseases are among the leading causes of musculoskeletal disability. For many types of tendinopathies, women have worse clinical outcomes than men. It is possible that sex-based differences in tendon morphology, composition and mechanical properties may explain the greater susceptibility of women to develop tendinopathies. Our objective was to evaluate the mechanical properties, biochemical composition, transcriptome, and cellular activity of plantarflexor tendons from four month old male and female C57Bl/6 mice using in vitro biomechanics, mass spectrometry-based proteomics, genome-wide expression profiling, and cell culture techniques. Differences between groups were tested using t-tests (α=0.05). While the Achilles tendons of male mice were approximately 6% larger than female mice (P<0.05), the cell density of female mice was around 19% larger than males (P<0.05). No significant differences in the length (P=0.34), peak force (P=0.86), peak stress (P=0.52) or energy loss during stretch (P=0.94) of plantaris tendons were observed. Mass spectrometry proteomics analysis revealed no significant difference between sexes in the abundance of major extracellular matrix (ECM) proteins like collagen types I (P=0.30) and III (P=0.68), but female mice had approximately two-fold elevations (P<0.05) in different minor ECM proteins such as fibronectin, periostin, and tenascin. Using microarray analysis, there was no significant differences (P>0.05) in the expression of most major and minor ECM genes, and in the expression of genes involved in tendon fibroblast specification or proliferation. Whole tendon qPCR analysis showed significant expression differences in elastin, scleraxis, and tenomodulin. Cell culture techniques to test the effects of sex-specific extracellular environment on cellular activity show significant differences in gene expression of type I and III collagen, Ki67, scleraxis, and tenomodulin. Histologic analysis demonstrated that males have larger tendon cross-sectional area and lower cell density when compared to females. However, there were no differences between the sexes in the mechanical properties of tendons or in the majority of primary structural extracellular matrix proteins, although elevations were observed in some minor ECM proteins. Microarray analysis also showed no significant sex-based differences in the expression of major genes associated with collagen composition, extracellular components and turnover, and fibroblast proliferation. Cell culture tests of non-autonomous cellular activity show no major signals for ECM synthesis nor fibroblast proliferation. Our results indicate that while male mice expectedly had larger tendons, male and female mice have very similar mechanical properties and biochemical composition, with small increases in minor ECM proteins and proteoglycans in female tendons. The role that these minor ECM proteins and proteoglycans play in tendon repair should be evaluated in future studies. No treatment administered, study done to evaluate normal expression profiles of male and female tenocytes. This analysis is based on a Mouse Gene ST 2.1 strip that was processed in the microarray facility in May 2015 using the wt-pico kit.
2016-08-11 | E-GEOD-85415 | biostudies-arrayexpress